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Front. Immunol. | doi: 10.3389/fimmu.2018.02981

High levels of Eomes promote exhaustion of anti-tumor CD8+ T cells

 Jing Li1, Yi He1, Jing Hao1,  Ling Ni1 and  Chen Dong2*
  • 1Institute for Immunology Tsinghua University, School of Medicine Tsinghua Univeristy, China
  • 2Immunology, Tsinghua University, China

Eomes, a T-box transcription factor, is known important for both function and homeostasis of effector and memory T cells, but was recently also implicated in CD8+ T cell exhaustion. However, whether and how Eomes might regulate effector functions or exhaustion of CD8+ T cells, especially in the tumor setting, is unknown. Here we first show, as tumor progressed, Eomes expression was elevated in tumor-infiltrating CD8+ T cells, especially in PD-1+Tim-3+ exhausted CD8+ T cells. Complete loss of Eomes in T cells resulted in impaired development of anti-tumor CTLs, whereas deletion of one allele of Eomes in T cells decreased development of exhausted CD8+ T cells, which offered better tumor control. Integrative analysis of RNAseq and ChIPseq of Eomes-overexpressing T cells revealed that high levels of Eomes expression directly controlled expression of T cell exhaustion genes, such as Havcr2. In addition, Eomes might compete with T-bet binding to regulatory genomic loci to antagonize T-bet functions. Collectively, Eomes exerts bimodal functions in CD8+ T cells in tumor.

Keywords: Eomes, transcription factor, t cell exhaustion, Cytotoxic T Cells, tumor immunity

Received: 23 Oct 2018; Accepted: 04 Dec 2018.

Edited by:

Wanjun Chen, National Institutes of Health (NIH), United States

Reviewed by:

Fernando A. Arosa, Universidade da Beira Interior, Portugal
Jinfang Zhu, National Institute of Allergy and Infectious Diseases (NIAID), United States  

Copyright: © 2018 Li, He, Hao, Ni and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Chen Dong, Tsinghua University, Immunology, Beijing, China,